Scientific Publications by FDA Staff
J Virol 2006 Dec;80(24):12141-8
Activation of microglia by Borna Disease Virus infection: an in vitro study.
Ovanesov MV, Sauder C, Rubin SA, Richt J, Nath A, Carbone KM, Pletnikov MV
Pletnikov MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Neurobiol, 600 N Wolfe St,CMSC 8-121, Baltimore, MD 21287 USA Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Div Neurobiol, Baltimore, MD 21287 USA US FDA, CBER, Bethesda, MD 20014 USA Natl Anim Dis Ctr, Ames, IA USA Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA
Neonatal Borna disease virus (BDV) infection of the rat brain is associated with microglial activation and damage to the certain neuronal populations. Since persistent BDV infection of neurons in vitro is non-cytolytic and non-cytopathic, activated microglia have been suggested to be responsible for neuronal cell death in vivo. However, the mechanisms of activation of microglia in neonatally BDV-infected rat brain have not been investigated. To address these issues, activation of primary rat microglial cells was studied following exposure to purified BDV, to persistently BDV-infected primary cortical neurons or after BDV infection of primary mixed neuron-glial cultures. Neither purified virus nor BDV-infected neurons alone activated primary microglia as assessed by the changes in cell shape or production of the pro-inflammatory cytokines. In contrast, in the BDV-infected primary mixed cultures, we observed proliferation of microglia cells that acquired the round-shape morphology and expressed major histocompatibility complex molecules of class I and II. These manifestations of microglia activation were observed in the absence of direct BDV infection of microglia or overt neuronal toxicity. In addition, compared to uninfected mixed cultures, activation of microglia in BDV-infected mixed cultures was associated with a significantly greater LPS-induced release of tumor necrosis factor-alpha, interleukin 1beta and interleukin 10. Taken together, the present data are the first in vitro evidence that persistent BDV infection of neurons and astrocytes rather than direct exposure to the virus or dying neurons is critical for activating microglia.
|Category: Journal Article|
|PubMed ID: #17020949|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-04||Entry Last Modified: 2012-08-29|